European journal of pain : EJP
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This study evaluated the antinociceptive effects of the selective and non-peptide CXCR2 antagonist SB225002 in mouse models of pain. As assessed in different tests of spontaneous nociception, intraperitoneal (i.p.) administration of SB225002 caused consistent and dose-related reduction of acetic acid-induced abdominal constrictions, whereas it did not significantly affect the nociception evoked by formalin, capsaicin, glutamate or phorbol ester acetate (PMA). Systemic treatment with SB225002 strikingly reduced the spontaneous nociception induced by 8-bromo-cAMP (8-Br-cAMP), or mechanical hypernociception induced by prostaglandin E(2) (PGE(2)), epinephrine, or the keratinocyte-derived chemokine (KC). ⋯ In the persistent models of pain evoked by complete Freund's adjuvant (CFA) or by the partial ligation of the sciatic nerve (PLSN), the repeated administration of SB225002 displayed prominent and long-lasting antinociceptive effects. Notably, SB225002 did not evoke unspecific central effects, as evaluated in the open-field and rota-rod tests, or even in the latency responses for thermal stimuli. Our data confirm the previous notion on the critical role exerted by chemokines in pain, indicating that selective CXCR2 antagonists, such as SB225002, might well represent interesting and innovative alternatives for the management of both acute and chronic pain.
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The impact of pain beliefs on coping and adjustment is well established. However, less is known about how beliefs unrelated to pain might impact upon this experience. In particular, just world beliefs could impact upon and be influenced by chronic pain, given that pain is not experienced in a vacuum but instead is experienced in a social context where justice issues are potentially salient. ⋯ When interaction terms relating to personal and general just world beliefs were entered simultaneously into regression analyses, the personal just world belief did not predict psychological distress. However, pain intensity positively predicted psychological distress at low but not high levels of the general just world belief, while disability predicted psychological distress at low and high levels of this belief. This suggests that a strong general just world belief has implications for psychological well-being in chronic pain, and as such this belief may occupy a potential coping function in this context.
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The analgesic effect of nitrous oxide (N(2)O) is thought to depend on noradrenaline release in the spinal cord following activation of descending inhibitory neurons. In addition to this indirect facilitation of inhibition in the spinal cord, we previously showed direct inhibition of glutamate receptors in dorsal horn neurons by N(2)O. Since general anesthetics could possibly affect excitatory and/or inhibitory components of synaptic transmission, we sought to evaluate the direct effect of N(2)O on inhibitory transmission in spinal cord neurons. ⋯ N(2)O did not affect the amplitude, frequency or decay time probability distribution of either GABA or glycine receptor-mediated miniature postsynaptic currents. We further sought to determine the effect of N(2)O on focal stimulation-evoked synaptic currents mediated by GABA and glycine receptors, and found no effect in the majority of neurons. These and other findings suggest that N(2)O has a discrete action in the spinal cord, distinct from the effects of the volatile anesthetics, consisting of inhibition of excitation in SG neurons through an action on ionotropic glutamatergic receptors and potentiation of inhibition through the descending noradrenergic system.
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Many patients with multiple sclerosis (MS) develop central neuropathic pain (CP). In the present study somatosensory abnormalities have been analysed in detail in 62 patients with MS and CP (42 women, 20 men; mean age 52 years) and in a control group of 10 women and 6 men (mean age 47 years) with MS and sensory symptoms, but without pain. Assessment included clinical testing and quantitative methods (QST) for the measurement of perception thresholds for touch, vibration, and temperatures. ⋯ Comparisons between painful and non-painful regions showed both the absolute threshold values and the index values to be significantly more abnormal, in the CP regions, for warmth (p<0.001), cold (p<0.05), difference limen (innoxious warmth and cold, p<0.01), cold pain (p<0.01) and heat pain/cold pain combined (p<0.001). Also the comparisons between regions with central pain and regions with sensory symptoms in the controls showed significantly more abnormal thresholds in the CP patients for warmth (p<0.05), cold (p<0.01), difference limen (innoxious warmth and cold, p<0.01) and heat pain/cold pain combined (p<0.001). The results support the general hypothesis that only patients who have lesions affecting the spinothalamo-cortical pathways run the risk of developing central pain.
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In our previous studies, psychological stress was shown to enhance operant escape responding of male and female rats. The stressors that produced hyperalgesia were physical restraint and social defeat. Nociceptive input also elicits stress reactions, generating the prediction that pain would facilitate pain under certain circumstances. ⋯ Similarly, escape from cold (10 degrees C) was enhanced when preceded by escapable 44.5 degrees C stimulation. Thus, prior nociceptive stimulation enhanced escape from aversive thermal stimulation. Facilitation of pain by a preceding pain experience is consistent with stress-induced hyperalgesia and contrasts with other models of pain inhibition by concurrent nociceptive stimulation.